Organics

16 pages, 3749 KB

Open AccessArticle

Integrated In Silico and Chromatographic Evaluation of the Biological Properties of Novel Bis-Substituted Thiocarbohydrazone Derivatives

by Suzana Apostolov, Dragana Mekić, Gorana Mrđan and Gyöngyi Vastag

Organics 2026, 7(2), 19; https://doi.org/10.3390/org7020019 - 12 May 2026

Abstract

Thiocarbohydrazone derivatives represent a highly significant class in medicinal chemistry, characterized by a versatile scaffold defined with a thiocarbonyl (C=S) core and one or two imine (–C=N–) functionalities, allowing for precise modulation of their physicochemical and biological properties. The biological potential of a series of novel bis-substituted thiocarbohydrazone derivatives was predicted and evaluated through comprehensive in silico analysis. All investigated compounds complied with Lipinski’s Rule of 5, with most also satisfying the Rule of 3 while simultaneously exhibiting favorable pharmacokinetic properties and low predicted ecotoxicity. To substantiate these findings and elucidate the influence of para-substituents, chromatographic behavior of the studied derivatives was evaluated using reversed-phase thin-layer chromatography (RP-TLC). Initial linear regression analysis revealed statistically significant correlations between chromatographic parameters and in silico-derived descriptors of lipophilicity, pharmacokinetics, and ecotoxicity. Furthermore, cluster analysis and principal component analysis provided a robust and unambiguous interpretation of the structure–property relationships, highlighting substituent polarity as the leading factor controlling the bioactivity of bis-substituted thiocarbohydrazones, although the contribution of electronic effects cannot be neglected. Moreover, R_M⁰ correlates with lipophilicity and pharmacokinetics, whereas m reflects ecotoxicity. Collectively, these findings emphasize the critical role of subtle structural variations in shaping the overall properties of these novel derivatives. Full article

► Show Figures

Figure 1

12 pages, 822 KB

Open AccessArticle

Synthesis of 23,23-Difluoro-24-nor- and 24′,24′-Difluoro-24-Homovitamin D₃ Analogues and Unexpected Structure-Activity Relationships

by Fumihiro Kawagoe, Hiroya Tabuchi, Taiyo Ideguchi, Yuki Okamoto, Souma Murata, Tomofumi Yatsu, Syota Yamada, Kaori Yasuda, Yusuke Akagi, Masashi Takano, Toshie Fujishima, Yoshiki Miyata, Ken’ichi Aoki, Toshiyuki Sakaki and Atsushi Kittaka

Organics 2026, 7(2), 18; https://doi.org/10.3390/org7020018 - 27 Apr 2026

Viewed by 264

Abstract

We synthesized two vitamin D₃ analogues, 3 and 4, which have a shortened or elongated fluoro-side-chain based on 24,24-difluoro-25-hydroxyvitamin D₃ (5) using an efficient convergent approach and studied their preliminary biological activity. Both analogues exhibited greater resistance to CYP24A1-mediated metabolism than the natural 25-hydroxyvitamin D₃ (6), although their stability was lower than that of 5. Analogue 3 showed an approximately 100-fold lower human vitamin D receptor (hVDR)-binding affinity compared with 5 and 6. Despite this marked reduction in VDR-binding affinity, it demonstrated an approximately 1.5-fold increase in VDR-ligand binding domain (LBD) transcriptional activation of the natural ligand 6. In contrast, analogue 4 displayed moderate VDR-binding affinity and VDR-LBD transactivation compared with 5 and 6. We found that compound 3 is a unique vitamin D analogue with a fluorinated and shortened side-chain, exhibiting low binding affinity for hVDR but potent transcriptional activity through VDR-LBD with its long half-life; thus, 3 may serve as a basic structural skeleton for advancing medicinal chemistry and drug discovery. Full article

► Show Figures

Figure 1

8 pages, 686 KB

Open AccessArticle

Revised Formal Total Synthesis of Dehydro-δ-Viniferin and Anigopreissin A

by Alessandro Santarsiere, Marianna Volgare and Lucia Chiummiento

Organics 2026, 7(2), 17; https://doi.org/10.3390/org7020017 - 16 Apr 2026

Viewed by 288

Abstract

This work presents a revised total synthesis of two pharmacologically relevant benzofurans using newly developed environmentally friendly methodologies. In particular, we focused on establishing improved synthetic routes to stilbene dimers under milder and more sustainable reaction conditions. During our investigations, we optimized an efficient Sonogashira coupling carried out in water, which, followed by a Suzuki-like reaction conducted in dimethyl carbonate (DMC) in the absence of any transition metals, served as the key step for the synthesis of the benzofuran core. Full article

► Show Figures

Figure 1

56 pages, 7096 KB

Open AccessReview

Recent Developments in Chemical Synthesis and Biological Activities of Aloe-Emodin Derivatives

by Jeltzlin Semerel, Nigel John, Pedro Fardim and Wim Dehaen

Organics 2026, 7(2), 16; https://doi.org/10.3390/org7020016 - 10 Apr 2026

Viewed by 291

Abstract

Aloe-emodin is an anthraquinone with a wide range of medicinal applications, including anti-angiogenic, anticancer, antimicrobial, antiviral, anti-inflammatory, and antioxidant activities. In this review, the functionalization of aloe-emodin using various synthetic methods, including alkylation, condensation, esterification, the Finkelstein reaction, and the Kabachnik–Fields reaction was reported. The biological activity of the synthesized aloe-emodin derivatives is discussed, with a focus on their potential future applications as anticancer agents, enzyme inhibitors, anti-inflammatory agents, and antimicrobial agents. This review also discusses the structure–activity relationship (SAR) and the mechanism of action (e.g., molecular docking studies, cell membrane-disrupting capacity, and apoptosis studies). This review highlights the many contributions made towards the design and development of novel, biologically active aloe-emodin derivatives. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

► Show Figures

Figure 1

35 pages, 10285 KB

Open AccessArticle

Synthesis, Characterization, and Multidimensional In Silico Evaluation of Novel Etodolac-Based 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents

by Tiba M. Hameed, Rafid M. Hashim, S. J. Abed, Raneen Hashim Ridha and O. Al-Mohammed Baqer

Organics 2026, 7(2), 15; https://doi.org/10.3390/org7020015 - 7 Apr 2026

Viewed by 515

Abstract

A new series of eight novel etodolac-based 1,3,4-oxadiazoles was synthesized, characterized, and tested in silico in multidimensional routes, starting with etodolac, a well-known nonsteroidal anti-inflammatory medication (NSAID). In silico studies were performed prior to synthesis using the molecular docking technique in CCDC GOLD suite software (2025.3) to assess the interactions with two key targets involved in cancer pathogenesis: the crystal structure of the epidermal growth factor receptor EGFR tyrosine kinase domain (PDB ID: 4HJO) and the matrix metalloproteinase (MMP-9) complex (PDB ID: 5CUH). ADME studies were performed to assess the physicochemical properties of the synthesized molecules. Importantly, biotransformation prediction also indicated that the derivatives possess high metabolic stability, with hydroxylation of the thio-ether group as the primary predicted biotransformation route. All compounds were characterized using melting point, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. In vitro and/or in vivo experiments are needed to confirm this preliminary anticancer study. Full article

(This article belongs to the Collection Advanced Research Papers in Organics)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Organics, Volume 7, Issue 2 (June 2026) – 5 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI